TY - JOUR
T1 - Platelet-activating factor (PAF) up-regulates plasma and tissue PAF- acetylhydrolase activity in the rat
T2 - Effect of cycloheximide
AU - Wang, Hao
AU - Tan, Xiao Di
AU - Qu, Xiao Wu
AU - Chang, Hong
AU - Remick, Daniel G.
AU - Gonzalez-Crussi, F.
AU - Hsueh, Wei
PY - 1997/11
Y1 - 1997/11
N2 - Platelet-activating factor (PAF) is a proinflammatory phospholipid mediator implicated in necrotizing enterocolitis. Regulation of PAF- acetylhydrolase (AH), the enzyme degrading PAF, is poorly understood. In this study we found that administration of a dose of PAF (1.5 μg/kg, i.v.), which does not cause gross intestinal injury, increased plasma and intestinal PAF- AH in the rat. Cycloheximide (CHX, 5 mg/kg, i.v.) reduced the activity of plasma (but not intestinal tissue) AH in control, as well as in PAF-injected rats, and aggravated systemic inflammation and tissue injury in the latter. The intestinal necrosis induced by PAF and CHX was ameliorated by posttreatment with WEB2170 (a PAF antagonist), indicating a role of endogenous PAF in mediating injury. Both WEB2170 and anti-TNF antibody reduced PAF-induced AH activity in intestinal tissue, but not in the plasma. Allopurinol largely prevented the injury induced by PAF and CHX, but had no effect on the up-regulation of AH. We conclude: 1) de novo protein synthesis is required to maintain physiologic AH level in the plasma: 2) PAF up- regulates plasma and intestinal AH activity; 3) CHX enhances the injurious effect of PAF; 4) endogenous PAF and TNF also play a role in the up- regulation of intestinal AH; the former probably mediating the intestinal injury by PAF; and 5) reactive oxygen species may mediate the injurious effect of PAF plus CHX, but do not contribute to the regulation of AH by PAF.
AB - Platelet-activating factor (PAF) is a proinflammatory phospholipid mediator implicated in necrotizing enterocolitis. Regulation of PAF- acetylhydrolase (AH), the enzyme degrading PAF, is poorly understood. In this study we found that administration of a dose of PAF (1.5 μg/kg, i.v.), which does not cause gross intestinal injury, increased plasma and intestinal PAF- AH in the rat. Cycloheximide (CHX, 5 mg/kg, i.v.) reduced the activity of plasma (but not intestinal tissue) AH in control, as well as in PAF-injected rats, and aggravated systemic inflammation and tissue injury in the latter. The intestinal necrosis induced by PAF and CHX was ameliorated by posttreatment with WEB2170 (a PAF antagonist), indicating a role of endogenous PAF in mediating injury. Both WEB2170 and anti-TNF antibody reduced PAF-induced AH activity in intestinal tissue, but not in the plasma. Allopurinol largely prevented the injury induced by PAF and CHX, but had no effect on the up-regulation of AH. We conclude: 1) de novo protein synthesis is required to maintain physiologic AH level in the plasma: 2) PAF up- regulates plasma and intestinal AH activity; 3) CHX enhances the injurious effect of PAF; 4) endogenous PAF and TNF also play a role in the up- regulation of intestinal AH; the former probably mediating the intestinal injury by PAF; and 5) reactive oxygen species may mediate the injurious effect of PAF plus CHX, but do not contribute to the regulation of AH by PAF.
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U2 - 10.1203/00006450-199711000-00008
DO - 10.1203/00006450-199711000-00008
M3 - Article
C2 - 9357930
AN - SCOPUS:0030728103
SN - 0031-3998
VL - 42
SP - 597
EP - 603
JO - Pediatric Research
JF - Pediatric Research
IS - 5
ER -